We are studying some of the mechanisms of metabolic heat production during cold adaptation in mammals. Small mammals adapt to cold by dramatic increases in heat production in conjunction with morphological and behavioral adjustments that conserve heat. The mechanisms causing such increases in heat production are not settled and it is the goal of this project to elucidate some of these mechanisms. The metabolic rate of tissue slices of cold-adapted rodents are higher than those of warm- adapted controls. In a preliminary experiment we have shown that the major fraction of the increase in oxygen uptake of tissue slices of cold-adapted mice was ouabain sensitive. I propose to extend the preliminary experiment with a series of experiments to study the following: 1. Show that the major source of elevated heat production of tissue slices of cold-adapted rodents is in fact due to increased activity of the sodium-pump. 2. Examine the time course of the response of stimulation of the sodium-pump and relate it to the time course of the metabolic response of the whole animal. 3. Determine whether or not the response can be elicited by cold temperature stimulation of the control area in the hypothalamus. 4. Determine the involvement of the thyroid gland and of nor-epinephrine in regulating the response to cold. 5. Compare the metabolic response of tissue slices to that of tissue homogenates during cold adaptation.